Introduction: When a patient enters the emergency room in a non-traumatic coma, immediate medical or surgical action must be taken. Therefore, understanding the most common causes of non-traumatic altered mental status (AMS) and related mortality may help with these patients’ care. Aim: The study aimed to examine the clinical characteristics of adult patients who report to the emergency room in an AMS but have no prior head injury. Materials and methods: A total of 112 patients who presented to our hospital with AMS were enrolled in this prospective observational study, which was conducted over a one-year and six-month period in the emergency department of a tertiary-care hospital. A previously created case registration form was used to gather clinical records of patients with AMS in the emergency room, including their demographics, medical history, signs and symptoms upon admission, diagnosis, clinical assessment techniques, and emergency management and outcome. Results: Most patients were men aged >40 years. The reasons for AMS were neurological, followed closely by metabolic and viral factors. The study indicates that bacterial meningoencephalitis, hepatic coma, organophosphorus (OP) poisoning, intoxication, infarcts, and intracerebral haemorrhage are the main causes of AMS and are associated with lower mortality. Conclusion: The most frequently encountered diagnostic categories causing AMS were primarily neurological, but they differed from similar studies, indicating significant variability in the aetiologies in studies conducted in diverse demographic settings and the need for large-scale, multicenter studies.